A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response.

Human tauopathies including Alzheimer's disease, progressive supranuclear palsy and related disorders, are characterized by deposition of pathological forms of tau, synaptic dysfunction and neuronal loss. We have previously identified a pathogenic C-terminal tau fragment (Tau35) that is associated with human tauopathy. However, it is not known how tau fragmentation affects critical molecular processes in cells and contributes to impaired physiological function.

Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuropathological deposits of amyloid plaques and neurofibrillary tangles comprised of β-amyloid and tau protein, respectively. In AD, tau becomes abnormally phosphorylated and aggregates to form intracellular deposits. However, the mechanisms by which tau exerts neurotoxicity in disease remain unclear.